MicroRNA-584-3p reduces the vasculogenic mimicry of human glioma cells by regulating hypoxia-induced ROCK1 dependent stress fiber formation
MicroRNA-584-3p reduces the vasculogenic mimicry of human glioma cells by regulating hypoxia-induced ROCK1 dependent stress fiber formation
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MicroRNA-584-3p 通过调节缺氧诱导的 ROCK1 依赖性应力纤维形成来减少人胶质瘤细胞的血管生成拟态
DOI：
10.4149/neo_2017_102
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发表时间：
2017-01-01
期刊：
影响因子：
3
通讯作者：
Li, G.
中科院分区：
文献类型：
--
作者：
Xu, S.;Zhang, J.;Li, G.
本研究报告了microRNA-584-3p(miR-584-3p)与人脑胶质瘤细胞的血管生成拟态(Vm)相关。不出所料，无Vm现象的胶质瘤患者术后生存时间显著长于Vm阳性患者。MIR-584-3p可能通过抑制恶性胶质瘤的Vm而发挥强大的肿瘤抑制作用。然而，这些特性背后的分子机制仍然知之甚少。我们的初步机制研究表明，miR-584-3p通过干扰低氧诱导的应激纤维的形成和胶质瘤细胞的迁移而抑制Vm。具体地说，我们将ROCK1定义为在胶质瘤细胞中参与这一过程的miR-584-3p的潜在功能相关靶点。我们的结果表明miR-584-3p在胶质瘤中具有肿瘤抑制功能，它通过拮抗缺氧诱导的ROCK1依赖的应激纤维的形成来抑制肿瘤细胞的Vm。我们的发现对以miR-584-3p为靶点的胶质瘤基因治疗具有潜在的意义，并提示Vm可作为胶质瘤的预后指标。
We report in this study that microRNA-584-3p (miR-584-3p) is related to the vasculogenic mimicry (VM) of human glioma cells. Unsurprisingly, the postoperative survival time was significantly prolonged in those glioma patients without VM phenomena compared with those with positive VM. miR-584-3p may function as a potent tumor suppressor by inhibiting VM of malignant glioma. However, the molecular mechanisms underlying these properties remain poorly understood. Our preliminary mechanistic studies revealed that miR-584-3p suppressed the VM by disturbing hypoxia-induced stress fiber formation and migration of glioma cells. Specifically, we defined ROCK1 as a potential functionally relevant target of miR-584-3p involved in this process in glioma cells. Our results demonstrate a tumor suppressor function for miR-584-3p in glioma, where it inhibits the VM of tumor cells by antagonizing hypoxia-induced ROCK1-dependent stress fiber formation. Our findings have potential implications for glioma gene therapy by targeting miR-584-3p and suggest that VM could represent a prognostic indicator for gliomas.